Eugenol- and Iodoform-Loaded Lipid Liquid Crystal Dressing for Alveolar Osteitis: Formulation, In Vitro Evaluation, and a Double-Blind Randomized Clinical Trial

Purpose: This study aimed to formulate and clinically evaluate a novel lipid liquid crystal (LLC) dressing containing eugenol and iodoform, designed for sustained release, antimicrobial activity, and pain relief in alveolar osteitis (AO). 

Methods: Formulations with varying ratios of phosphatidylcholine (PC), sorbitan monooleate (SMO), glyceryl monooleate (GMO), and N-methyl-2-pyrrolidone (NMP) were prepared. The formulation which showed a good physicochemical stability and suitable viscosity was selected for further studies (F17, the optimized formulation). The optimized formulation was characterized for physicochemical properties and in vitro release. In a double-blind, randomized trial with 60 AO patients, the LLC-dressing was compared to Alvogyl^® for pain, analgesic use, and dressing applications over seven days. 

Results: The optimized formulation (F17) contained 35.25% PC, 35.25% SMO, 13.7% eugenol, and 15.8% iodoform, demonstrating an improved sustained drug release profile, appropriate viscosity, effective antibacterial activity, 100% encapsulation efficiency, and drug loading of 13.7% (eugenol) and 15.8% (iodoform). Visual Analog Scale (VAS) pain scores were comparable between LLC-dressing and Alvogyl^® at all assessed time points, with no significant differences (0 h: 8.14 ± 1.40 vs. 7.96 ± 1.02; 7 days: 0.70 ± 0.66 vs. 0.78 ± 0.60; p > 0.05). Analgesic use (5.51 ± 3.06 vs. 6.13 ± 2.87, P = 0.401) and dressing applications (2.27 ± 1.12 vs. 2.57 ± 1.20, P = 0.345) showed similar efficiency. 

Conclusion: The optimized LLC-dressing (F17) exhibits favorable physicochemical and in vitro characteristics and may be considered a potential alternative to Alvogyl^® for the management of AO.